The present invention relates to an extended focal region measurement apparatus and method, for application especially, but not exclusively, to the investigation of the structure and composition of regions of the human body.
Diabetes is a major and rapidly growing problem: there are estimates that over 170 million people suffer from the disorder worldwide. In addition, studies have shown that the incidence of juvenile-onset, insulin-dependent diabetes has doubled over the last 15 years. There has also been a doubling in the number of children under the age of 5 suffering from diabetes in just 10 years.
The symptoms associated with diabetes can be severe. If the blood glucose level is not suitably controlled by the patient, the physical damage which may be caused includes blindness, heart disease and gangrene. As such, the mortality rate for diabetics is significantly higher than the rate for the average person.
A person's blood glucose concentration varies over a relatively short timescale, due to a number of factors, such as the length of time since the patient's last meal, the type of food ingested, the amount of exercise taken, and whether or not the patient is otherwise ill. As a result, diabetics usually need to test their glucose levels many times a day, in order to monitor and control their condition. The actual testing regime varies between patients and is individually prescribed by the doctor or diabetes educator of the patient.
The primary method used for testing blood glucose concentration involves the taking of a blood sample, which is then analysed. In this test, a patient's finger or arm is pricked with a small needle and the resulting drop of blood is placed on a test strip, for analysis in a hand-held meter. If the glucose concentration reading is above an acceptable level, insulin must be injected into the blood stream to bring the glucose concentration back within an acceptable range.
Because of the frequency of testing required to monitor the blood glucose concentration, the patient is normally expected to perform the tests throughout the day, drawing and analysing the blood sample himself. There are a number of problems experienced by patients with the above procedure. Firstly, the technique is invasive and therefore carries the risk of infection. Secondly, continual pricking of the fingers causes hard skin. Thirdly, the process is clearly not pain-free. Finally, there is a large, ongoing consumables cost associated with this method. As a result of these and other problems, certain sectors of the diabetic population do not test themselves as often as required. This is particularly the case for the elderly, who tend to lack the fine motor skills required; teenagers, who tend to find the whole procedure socially embarrassing; and children, who tend not to accept the discomfort associated with the process.
A number of non-invasive blood glucose concentration measuring techniques have been proposed to overcome these problems. One particular approach which has been suggested involves measuring the glucose concentration of the aqueous humor in the anterior chamber of the eye, since, while varying between individuals, there is a close correlation between this concentration and the blood glucose concentration. Measurement of the glucose concentration of the aqueous humor may be achieved by various means; for example, by polarimetry (e.g., U.S. Pat. No. 5,896,198); by Raman techniques (e.g., WO-A-00/02479); by spectrometry (e.g., U.S. Pat. No. 5,969,815); or by reflectometry (e.g., U.S. Pat. No. 6,236,089).
A desirable alternative approach to measuring the glucose concentration in the aqueous humor involves measuring the refractive index of the aqueous humor, since there is a strong correlation between the refractive index and the glucose concentration.
U.S. Pat. No. 3,963,019 discloses a method and apparatus, by which a beam of light is projected into and through the aqueous humor of a patient's eye. The angular displacement of light reflected from the iris and through the aqueous humor is proportional to the refractive index of the aqueous humor. Hence by measuring the angle of the reflected light, the glucose concentration of the aqueous humor may be found. In practice, this technique measures the combined optical properties of the aqueous humor and the cornea and it is not trivial to deconvolve the effect of each. In addition, changes to the cornea, for example, will reduce the accuracy of readings taken in this way.
U.S. Pat. No. 6,152,875 discloses a method and apparatus, by which the refractive index of the aqueous humor may be derived by measuring the intensity of light reflected from the eye. The intensities of reflected light from the air/cornea and cornea/aqueous humor interfaces are measured and compared to determined how much light is reflected from the cornea/aqueous humor interface relative to the cornea/air interface. It is assumed that the amount of light reflected from the air/cornea interface is constant and that the amount of light reflected from the cornea/aqueous humor interface is related to the refractive index of the aqueous humor. There are a number of practical limitations to this technique. For example, any stray light or reflections from other surfaces will cause inaccuracies in measurements, so additional steps such as interferometry, frequency shift, or ultra-short pulses are required to achieve the required accuracy. Since the method relies on the measurement of the relative reflected intensities from two surfaces of the eye, further inaccuracies may be introduced because of diurnal variations in the shape of the cornea, changes in the refractive index of the tear film (itself affected by the blood glucose level) and variations in atmospheric conditions, such as temperature and pressure, which will alter the refractive index of the air.
WO-A-03/025562 discloses an interferometric technique for measuring the refractive index of the aqueous humor. In this technique, two beams of light are shone onto the iris in the eye, one beam having a plane wavefront and the other beam having a spherical wavefront. The two beams interfere where they coincide on the iris, to form a pattern of dark and light rings at a detector. Changes in the refractive index of the aqueous humor affect the phase difference between the interfering beams and therefore the spacing of the fringes. The refractive index may thus be determined by measuring the spacing of the fringes. One practical problem with this technique is that a laser is required. A further problem is that interferometry is very sensitive to vibrations, with the result that the apparatus effectively needs to be arranged on an optical bench. In particular, this technique would not be suitable for use with a hand-held meter. Furthermore, with this interferometric arrangement, it is not possible to distinguish between corneal changes and changes in the aqueous humor.
There is a need, therefore, for an apparatus and method which employs a non-invasive, optical technique for the reliable determination of changes in the refractive index of the aqueous humor in the anterior chamber of an eye. In particular, it would be desirable for measurements made by such apparatus and method to be used to derive the concentration of glucose in the aqueous humor and, in turn, the concentration of glucose in the blood of a patient. There is also a need for an apparatus and method which may be used to determine the concentrations of other compounds in the aqueous humor, including both naturally occurring and intentionally introduced chemicals, and which may be used to measure other properties of the eye, such as corneal thickness. It would also be desirable for such an apparatus and method to find application additionally in the investigation of structures in other regions of the body.
The present invention aims to address the above and other objectives by providing an improved technique for the measurement of regions of a human or animal body and in particular properties of an eye.
According to a first aspect of the present invention, there is provided a method of measuring an apparent depth of a section of an animal body, the section being defined by first and second interfaces, comprising the steps: a) focusing a monochromatic incident beam of light to a plurality or continuum of measurement locations along a measurement line passing through the section, the measurement line being generated by an optical element adapted to provide an extended focal region for monochromatic light, such that incident light is focused to all measurement locations along the measurement line concurrently; b) detecting light reflected from at least one of the plurality of measurement locations when a respective interface is coincident therewith; c) generating at least a first and a second signal representative of the detected light reflected from the first and second interfaces respectively; and d) deriving from the first and second signals the apparent positions of the first and second interfaces.
When an extended focal region is generated within a region of the body, in particular the eye, incident light is reflected as a local peak when an interface between two media of different refractive indices is coincident with part of the extended focal region. By recording the signal generated by a detector on receipt of this reflected light, a reflected light intensity profile may be obtained. The signal is associated with the apparent position of the measurement location, either in time or space, so that the apparent depth of the section may be derived. The apparent depth will typically differ from the real, or physical, depth of the section by the refractive index of the section. Changes in the apparent depth may therefore be used to calculate changes in the refractive index of the section. For example, if the apparent depth is an optical path length through the aqueous humor, a change in the refractive index of the aqueous humor may be derived from a comparison of optical path length measurements, thereby providing a measure of the glucose concentration of the aqueous humor. In this case, the first and second surfaces are the cornea-aqueous humor interface and the aqueous humor-ocular lens interface respectively. Although the method and apparatus of the present invention are intended to be used predominantly with the human eye, the invention may also be applied to animal eyes or to other parts of human or animal bodies.
The present invention provides many advantages over previous techniques. For example, the present invention is capable of providing very high axial resolution (tens of nanometre). In addition, it is not necessary to measure the absolute intensity of the reflected light; the signal profile is instead used primarily to determine the apparent positions of the interfaces of the eye or other parts of the body. As such, the method is relatively less affected by atmospheric conditions and other changes to the outside of the eye. Furthermore, corneal changes, for example, may be de-convolved from the measurement of the apparent depth of the section. Also, a laser source is not essential for the present invention. Finally, scanning of the measurement region is not required enabling the measurement to be performed more quickly and the instrument to be more robust.
According to a second aspect of the present invention, there is provided an apparatus for measuring an apparent depth of a section of an animal body, the section being defined by first and second interfaces, comprising: a) an optical focusing assembly, comprising an optical element adapted to provide an expanded focal region for monochromatic light, the optical focusing assembly being adapted to focus an monochromatic incident beam of light to a plurality or continuum of measurement locations along a measurement line passing through the section, such that incident light is focused to all measurement locations along the measurement line concurrently; b) a detector assembly, adapted to detect light reflected from at least one of the plurality of measurement locations when a respective interface is coincident therewith and to generate a signal representative of that detected light; and c) a processor in communication with the detector assembly and adapted to receive from the detector assembly first and second signals corresponding to detected light reflected from the first and second interfaces respectively and to derive therefrom apparent positions of the first and second interfaces.
In preferred embodiments, the apparatus employs a confocal arrangement, so that the location from which the light is reflected may be precisely determined. In one embodiment the measurement location is scanned by translating a spatial filter on a scanning stage. In a preferred embodiment the extended focal region is obtained by focussing light with an axicon element.
According to a third aspect of the present invention, there is provided a method of measuring a property of an eye or other part of the body, comprising the steps of: a) generating an extended focal region within or proximate to the measurement region of interest; b) receiving reflected light from the measurement region; c) spatially filtering the reflected light in order to define a point location with the measurement region; d) scanning the measurement point with that region; e) measuring the intensity of reflected light received from each measurement point; f) relating an intensity measurement to an apparent position of the measurement location; g) selecting intensity measurements of interest representing measurement locations of interest; and h) determining a distance between the measurement locations of interest.
Preferably the measurement employs a spatial filter in the detector section that is confocal with the measurement point under investigation. Preferably the intensity measurements of interest are peaks in the reflected light intensity profile that is obtained, each peak representing a respective interface between different refractive regions of the eye or part of the body under investigation.
According to a fourth aspect of the present invention, there is provided an apparatus for measuring a property of an eye or other part of the body, comprising: a light source, a source optical element, adapted to direct light from the light source to the measurement location, an optical element adapted to give an extended focal region at the measurement location; a return optical element adapted to receive reflected light from the measurement location and to focus the reflected light to a receiver assembly, an optical detector, adapted to measure an intensity of the light received from each measurement position; and a processor, adapted to relate an intensity measurement to an apparent position of the measurement location, such that an apparent distance between measurement locations of interest, represented by respected intensity measurements of interest, may be derived.
Preferably, the apparatus employs a confocal scanning arrangement. Advantageously, a reference location is provided by a pinhole aperture, which also acts to stop stray light (i.e. light not reflected from the measurement position) from impinging on the detector.
The apparatus of the present invention may be used in a variety of applications. Preferably, the apparatus is compact and portable. In particular, the apparatus of the present invention may be formed of components using micro-electromechanical systems (MEMS), or micro-systems technology (MST), and may additionally or alternatively be incorporated in a hand-held device, and these features represent further aspects of the present invention.
Other preferred features are set out in the description, and in the dependent claims which are appended hereto.